T3DB: Buspirone

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (10)XML

Targets (10)

Record Information

Version

2.0

Creation Date

2009-07-21 20:27:01 UTC

Update Date

2014-12-24 20:25:51 UTC

Accession Number

T3D2807

Identification

Common Name

Buspirone

Class

Small Molecule

Description

Buspirone is only found in individuals that have used or taken this drug. It is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. Buspirone binds to 5-HT type 1A serotonin receptors on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus, thus inhibiting the firing rate of 5-HT-containing neurons in the dorsal raphe. Buspirone also binds at dopamine type 2 (DA2) receptors, blocking presynaptic dopamine receptors. Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. The net result of buspirone actions is that serotonergic activity is suppressed while noradrenergic and dopaminergic cell firing is enhanced.

Compound Type

Amide
Amine
Anti-Anxiety Agent
Anxiolytic
Drug
Hypnotic and Sedative
Metabolite
Organic Compound
Serotonin Agonist
Serotonin Receptor Agonist
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
8-(4-(4-(2-Pyrimidinyl)-1-piperizinyl)butyl)-8-azaspiro(4,5)decane-7,9-dione
Ansial
Anxiron
Anxut
Bespar
Buscalm
Busp
Buspar
Buspiron
Buspirona
Buspironum
Buspon
Dalpas
Epsilat
Pasrin
Spamilan

Chemical Formula

C₂₁H₃₁N₅O₂

Average Molecular Mass

385.503 g/mol

Monoisotopic Mass

385.248 g/mol

CAS Registry Number

36505-84-7

IUPAC Name

8-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-8-azaspiro[4.5]decane-7,9-dione

Traditional Name

buspirone

SMILES

O=C1CC2(CCCC2)CC(=O)N1CCCCN1CCN(CC1)C1=NC=CC=N1

InChI Identifier

InChI=1S/C21H31N5O2/c27-18-16-21(6-1-2-7-21)17-19(28)26(18)11-4-3-10-24-12-14-25(15-13-24)20-22-8-5-9-23-20/h5,8-9H,1-4,6-7,10-17H2

InChI Key

InChIKey=QWCRAEMEVRGPNT-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Diazinanes

Sub Class

Piperazines

Direct Parent

N-arylpiperazines

Alternative Parents

Substituents

Azaspirodecanedione
N-arylpiperazine
Azaspirodecane
Piperidinedione
Dialkylarylamine
Aminopyrimidine
N-alkylpiperazine
Piperidinone
Delta-lactam
Pyrimidine
Piperidine
Carboxylic acid imide, n-substituted
Heteroaromatic compound
Carboxylic acid imide
Dicarboximide
Amino acid or derivatives
Tertiary aliphatic amine
Tertiary amine
Lactam
Azacycle
Carboxylic acid derivative
Organic oxide
Organonitrogen compound
Organooxygen compound
Amine
Carbonyl group
Organic oxygen compound
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

N-arylpiperazine (CHEBI:3223 )
pyrimidines (CHEBI:3223 )
N-alkylpiperazine (CHEBI:3223 )
piperidones (CHEBI:3223 )
azaspiro compound (CHEBI:3223 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

EC 3.4.21.26 (prolyl oligopeptidase) inhibitor

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	201.5-202.5°C
Boiling Point	Not Available
Solubility	21.4 mg/L
LogP	2.63

Predicted Properties

Property	Value	Source
Water Solubility	0.59 g/L	ALOGPS
logP	1.95	ALOGPS
logP	1.78	ChemAxon
logS	-2.8	ALOGPS
pKa (Strongest Basic)	7.62	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	69.64 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	108.89 m³·mol⁻¹	ChemAxon
Polarizability	44.12 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-056r-3930000000-f72780a741e10d32e14d	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-000f-0930000000-081eac0a05abab8fc5fa	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0009000000-429c277f63eb2ab52f57	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0009000000-170a03c9244dada2609b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00di-0922000000-80c9aa9ae15b661116ad	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00di-1900000000-fafa91d49f01314afdf1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00dj-4900000000-460409b07d20201af414	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-000f-0930000000-081eac0a05abab8fc5fa	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-00di-1900000000-1548c934ed4552c550c0	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-00di-4900000000-3f738f9b3afda733fdbb	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-00di-0923000000-0432dbe18a87c4f8aac9	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-00ea-9600000000-c19888c809dc5e1e4345	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-00ea-9600000000-306c03950ac42645d650	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-00dj-4900000000-460409b07d20201af414	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-00di-1900000000-cd100d009ef3ee04589b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-00di-1900000000-fafa91d49f01314afdf1	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-00di-0922000000-80c9aa9ae15b661116ad	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-00di-0910000000-cf8501b071281e076ac4	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-000i-0009000000-f8f22927f54be6364e82	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-00di-3900000000-1b0646e8d778da56bd8e	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0029000000-e01810fdca67d6848abc	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0079-5679000000-e3b3f87f2a5001651596	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-8940000000-0f2042c84fa52ff07a00	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-0309000000-0cb92cbc3313c049e2b4	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0159-0905000000-852ca5ee117750d57ba3	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014i-4910000000-ae14188467b44ba1ea96	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-004i-6940000000-197b8ea9ac79cbda753b	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Oral. Rapidly absorbed in man. Bioavailability is low and variable (approximately 5%) due to extensive first pass metabolism.

Mechanism of Toxicity

Buspirone binds to 5-HT type 1A serotonin receptors on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus, thus inhibiting the firing rate of 5-HT-containing neurons in the dorsal raphe. Buspirone also binds at dopamine type 2 (DA2) receptors, blocking presynaptic dopamine receptors. Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. The net result of buspirone actions is that serotonergic activity is suppressed while noradrenergic and dopaminergic cell firing is enhanced.

Metabolism

Metabolized hepatically, primarily by oxidation by cytochrome P450 3A4 producing several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP) Route of Elimination: In a single-dose study using 14C-labeled buspirone, 29% to 63% of the dose was excreted in the urine within 24 hours, primarily as metabolites; fecal excretion accounted for 18% to 38% of the dose. Half Life: 2-3 hours (although the action of a single dose is much longer than the short halflife indicates).

Toxicity Values

LD50: 136 mg/kg (Oral, rat)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the management of anxiety disorders or the short-term relief of the symptoms of anxiety, and also as an augmention of SSRI-treatment against depression.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Symptoms of overdose include dizziness, drowsiness, nausea or vomiting, severe stomach upset, and unusually small pupils.

Treatment

General symptomatic and supportive measures should be used along with immediate gastric lavage. Respiration, pulse, and blood pressure should be monitored as in all cases of drug overdosage. No specific antidote is known to buspirone, and dialyzability of buspirone has not been determined. (2)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

608902

ChEBI ID

3223

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Buspirone

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Buspirone

References

Synthesis Reference

DrugSyn.org

MSDS

Link

General References

Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 5-hydroxytryptamine receptor 1A

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:: HTR1A
Uniprot ID:: P08908
Molecular Weight:: 46106.335 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0031 uM	Not Available	BindingDB 50001859
Inhibitory	0.00398 uM	Not Available	BindingDB 50001859
Inhibitory	0.0066 uM	Not Available	BindingDB 50001859
Inhibitory	0.015 uM	Not Available	BindingDB 50001859
Inhibitory	0.01513 uM	Not Available	BindingDB 50001859
Inhibitory	0.017 uM	Not Available	BindingDB 50001859
Inhibitory	0.01905 uM	Not Available	BindingDB 50001859
Inhibitory	0.02 uM	Not Available	BindingDB 50001859
Inhibitory	0.021 uM	Not Available	BindingDB 50001859
Inhibitory	0.0211 uM	Not Available	BindingDB 50001859
Inhibitory	0.02137 uM	Not Available	BindingDB 50001859
Inhibitory	0.024 uM	Not Available	BindingDB 50001859
Inhibitory	0.03 uM	Not Available	BindingDB 50001859
Inhibitory	0.07762 uM	Not Available	BindingDB 50001859
Inhibitory	0.212 uM	Not Available	BindingDB 50001859
Inhibitory	0.21379 uM	Not Available	BindingDB 50001859
IC50	0.025 uM	Not Available	BindingDB 50001859

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
de Boer SF, Lesourd M, Mocaer E, Koolhaas JM: Selective antiaggressive effects of alnespirone in resident-intruder test are mediated via 5-hydroxytryptamine1A receptors: A comparative pharmacological study with 8-hydroxy-2-dipropylaminotetralin, ipsapirone, buspirone, eltoprazine, and WAY-100635. J Pharmacol Exp Ther. 1999 Mar;288(3):1125-33. [10027850 ]
Rehman J, Kaynan A, Christ G, Valcic M, Maayani S, Melman A: Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor. Brain Res. 1999 Mar 13;821(2):414-25. [10064829 ]
Liang KC: Pre- or post-training injection of buspirone impaired retention in the inhibitory avoidance task: involvement of amygdala 5-HT1A receptors. Eur J Neurosci. 1999 May;11(5):1491-500. [10215901 ]
Becker C, Hamon M, Benoliel JJ: Prevention by 5-HT1A receptor agonists of restraint stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat. Neuropharmacology. 1999 Apr;38(4):525-32. [10221756 ]
Dupuis DS, Tardif S, Wurch T, Colpaert FC, Pauwels PJ: Modulation of 5-HT1A receptor signalling by point-mutation of cysteine351 in the rat Galpha(o) protein. Neuropharmacology. 1999 Jul;38(7):1035-41. [10428422 ]
Tandon M, O'Donnell MM, Porte A, Vensel D, Yang D, Palma R, Beresford A, Ashwell MA: The design and preparation of metabolically protected new arylpiperazine 5-HT1A ligands. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1709-12. [15026055 ]
Romero AG, Leiby JA, McCall RB, Piercey MF, Smith MW, Han F: Novel 2-substituted tetrahydro-3H-benz[e]indolamines: highly potent and selective agonists acting at the 5-HT1A receptor as possible anxiolytics and antidepressants. J Med Chem. 1993 Jul 23;36(15):2066-74. [8101876 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
Moon MW, Morris JK, Heier RF, Chidester CG, Hoffmann WE, Piercey MF, Althaus JS, Von Voigtlander PF, Evans DL, Figur LM, et al.: Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds. J Med Chem. 1992 Mar 20;35(6):1076-92. [1348089 ]
Dounay AB, Barta NS, Bikker JA, Borosky SA, Campbell BM, Crawford T, Denny L, Evans LM, Gray DL, Lee P, Lenoir EA, Xu W: Synthesis and pharmacological evaluation of aminopyrimidine series of 5-HT1A partial agonists. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1159-63. doi: 10.1016/j.bmcl.2008.12.087. Epub 2008 Dec 25. [19147349 ]
Zajdel P, Subra G, Bojarski AJ, Duszynska B, Pawlowski M, Martinez J: Arylpiperazines with N-acylated amino acids as 5-HT1A receptor ligands. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3406-10. Epub 2006 May 3. [16677812 ]
Becker OM, Dhanoa DS, Marantz Y, Chen D, Shacham S, Cheruku S, Heifetz A, Mohanty P, Fichman M, Sharadendu A, Nudelman R, Kauffman M, Noiman S: An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. J Med Chem. 2006 Jun 1;49(11):3116-35. [16722631 ]
Liu Z, Zhang H, Ye N, Zhang J, Wu Q, Sun P, Li L, Zhen X, Zhang A: Synthesis of dihydrofuroaporphine derivatives: identification of a potent and selective serotonin 5-HT 1A receptor agonist. J Med Chem. 2010 Feb 11;53(3):1319-28. doi: 10.1021/jm9015763. [20041669 ]
Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [21486038 ]
Sundaram H, Newman-Tancredi A, Strange PG: Characterization of recombinant human serotonin 5HT1A receptors expressed in Chinese hamster ovary cells. [3H]spiperone discriminates between the G-protein-coupled and -uncoupled forms. Biochem Pharmacol. 1993 Mar 9;45(5):1003-9. [8461029 ]
Hamon M, Lanfumey L, el Mestikawy S, Boni C, Miquel MC, Bolanos F, Schechter L, Gozlan H: The main features of central 5-HT1 receptors. Neuropsychopharmacology. 1990 Oct-Dec;3(5-6):349-60. [2078271 ]

Target Details

2. D(2) dopamine receptor

General Function:: Potassium channel regulator activity
Specific Function:: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:: DRD2
Uniprot ID:: P14416
Molecular Weight:: 50618.91 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.013 uM	Not Available	BindingDB 50001859
Inhibitory	0.09 uM	Not Available	BindingDB 50001859

References

Malt EA, Olafsson S, Aakvaag A, Lund A, Ursin H: Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls. J Affect Disord. 2003 Jun;75(1):77-82. [12781354 ]
Boido A, Boido CC, Sparatore F: Synthesis and pharmacological evaluation of aryl/heteroaryl piperazinyl alkyl benzotriazoles as ligands for some serotonin and dopamine receptor subtypes. Farmaco. 2001 Apr;56(4):263-75. [11421254 ]
Nader MA, Hannemann M: Interactions of buspirone or gepirone with nicotine on schedule-controlled behavior of pigeons. Behav Pharmacol. 1993 Jun;4(3):263-268. [11224194 ]
Pache DM, Fernandez-Perez S, Sewell RD: Buspirone differentially modifies short-term memory function in a combined delayed matching/non-matching to position task. Eur J Pharmacol. 2003 Sep 23;477(3):205-11. [14522358 ]
Fernandez-Perez S, Pache DM, Sewell RD: Co-administration of fluoxetine and WAY100635 improves short-term memory function. Eur J Pharmacol. 2005 Oct 17;522(1-3):78-83. Epub 2005 Oct 7. [16214127 ]
Romero AG, Leiby JA, McCall RB, Piercey MF, Smith MW, Han F: Novel 2-substituted tetrahydro-3H-benz[e]indolamines: highly potent and selective agonists acting at the 5-HT1A receptor as possible anxiolytics and antidepressants. J Med Chem. 1993 Jul 23;36(15):2066-74. [8101876 ]
Becker OM, Dhanoa DS, Marantz Y, Chen D, Shacham S, Cheruku S, Heifetz A, Mohanty P, Fichman M, Sharadendu A, Nudelman R, Kauffman M, Noiman S: An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. J Med Chem. 2006 Jun 1;49(11):3116-35. [16722631 ]
Kawakubo H, Takagi S, Yamaura Y, Katoh S, Ishimoto Y, Nagatani T, Mochizuki D, Kamata T, Sasaki Y: (R)-1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines: novel optically active compounds with strong 5-HT1A receptor binding ability exhibiting anticonflict activity and lessening of memory impairment. J Med Chem. 1993 Nov 12;36(23):3526-32. [7902439 ]

Target Details

3. 5-hydroxytryptamine receptor 2A

General Function:: Virus receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:: HTR2A
Uniprot ID:: P28223
Molecular Weight:: 52602.58 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.13803 uM	Not Available	BindingDB 50001859
Inhibitory	0.851 uM	Not Available	BindingDB 50001859

References

Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):621-9. [9225287 ]
Bojarski AJ, Kuran B, Kossakowski J, Koziol A, Jagiello-Wojtowicz E, Chodkowska A: Synthesis and serotonin receptor activity of the arylpiperazine alkyl/propoxy derivatives of new azatricycloundecanes. Eur J Med Chem. 2009 Jan;44(1):152-64. doi: 10.1016/j.ejmech.2008.03.019. Epub 2008 Apr 8. [18486277 ]

Target Details

4. Sigma non-opioid intracellular receptor 1

General Function:: Opioid receptor activity
Specific Function:: Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:: SIGMAR1
Uniprot ID:: Q99720
Molecular Weight:: 25127.52 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.036 uM	Not Available	BindingDB 50001859
IC50	0.263 uM	Not Available	BindingDB 50001859

References

Myers AM, Charifson PS, Owens CE, Kula NS, McPhail AT, Baldessarini RJ, Booth RG, Wyrick SD: Conformational analysis, pharmacophore identification, and comparative molecular field analysis of ligands for the neuromodulatory sigma 3 receptor. J Med Chem. 1994 Nov 25;37(24):4109-17. [7990111 ]
Perrone R, Berardi F, Colabufo NA, Leopoldo M, Tortorella V, Fiorentini F, Olgiati V, Ghiglieri A, Govoni S: High affinity and selectivity on 5-HT1A receptor of 1-aryl-4-[1-tetralin)alkyl]piperazines. 2. J Med Chem. 1995 Mar 17;38(6):942-9. [7699710 ]

Target Details

5. 5-hydroxytryptamine receptor 2B

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:: HTR2B
Uniprot ID:: P41595
Molecular Weight:: 54297.41 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.21379 uM	Not Available	BindingDB 50001859

References

Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):621-9. [9225287 ]

Target Details

6. 5-hydroxytryptamine receptor 2C

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:: HTR2C
Uniprot ID:: P28335
Molecular Weight:: 51820.705 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.48977 uM	Not Available	BindingDB 50001859

References

Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):621-9. [9225287 ]

Target Details

7. 5-hydroxytryptamine receptor 3A

General Function:: Voltage-gated potassium channel activity
Specific Function:: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
Gene Name:: HTR3A
Uniprot ID:: P46098
Molecular Weight:: 55279.835 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>10 uM	Not Available	BindingDB 50001859

References

Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [21486038 ]

Target Details

8. Multidrug and toxin extrusion protein 1

General Function:: Monovalent cation:proton antiporter activity
Specific Function:: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:: SLC47A1
Uniprot ID:: Q96FL8
Molecular Weight:: 61921.585 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	1.7 uM	Not Available	BindingDB 50001859

References

Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

Target Details

9. Multidrug and toxin extrusion protein 2

General Function:: Drug transmembrane transporter activity
Specific Function:: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:: SLC47A2
Uniprot ID:: Q86VL8
Molecular Weight:: 65083.915 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	46 uM	Not Available	BindingDB 50001859

References

Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

Target Details

10. Solute carrier family 22 member 2

General Function:: Quaternary ammonium group transmembrane transporter activity
Specific Function:: Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:: SLC22A2
Uniprot ID:: O15244
Molecular Weight:: 62579.99 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	12 uM	Not Available	BindingDB 50001859

References

Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

Buspirone (T3D2807)

Structure for T3D2807: Buspirone

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